rs35544003

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001379180.1(ESRRB):c.144C>A(p.Ile48Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0647 in 1,613,444 control chromosomes in the GnomAD database, including 4,914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.076 ( 605 hom., cov: 33)

Exomes 𝑓: 0.063 ( 4309 hom. )

Consequence

ESRRB
NM_001379180.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.310

Publications

17 publications found

Variant links:

Genes affected

ESRRB (HGNC:3473): (estrogen related receptor beta) This gene encodes a protein with similarity to the estrogen receptor. Its function is unknown; however, a similar protein in mouse plays an essential role in placental development. [provided by RefSeq, Jul 2008]

ESRRB Gene-Disease associations (from GenCC):

autosomal recessive nonsyndromic hearing loss 35
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
nonsyndromic genetic hearing loss
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ESRRB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.23).

BP6

Variant 14-76439434-C-A is Benign according to our data. Variant chr14-76439434-C-A is described in ClinVar as [Benign]. Clinvar id is 45001.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.31 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESRRB	NM_001379180.1 link	c.144C>A	p.Ile48Ile	synonymous_variant	Exon 2 of 7	ENST00000644823.1	NP_001366109.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESRRB	ENST00000644823.1 link	c.144C>A	p.Ile48Ile	synonymous_variant	Exon 2 of 7		NM_001379180.1	ENSP00000493776.1		A0A2R8Y491

Frequencies

GnomAD3 genomes

AF:

0.0762

AC:

11603

AN:

152184

Hom.:

601

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0918

Gnomad AMI

AF:

0.0603

Gnomad AMR

AF:

0.0855

Gnomad ASJ

AF:

0.0271

Gnomad EAS

AF:

0.256

Gnomad SAS

AF:

0.137

Gnomad FIN

AF:

0.0526

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0537

Gnomad OTH

AF:

0.0626

GnomAD2 exomes

AF:

0.0869

AC:

21504

AN:

247442

AF XY:

0.0861

show subpopulations

Gnomad AFR exome

AF:

0.0902

Gnomad AMR exome

AF:

0.0905

Gnomad ASJ exome

AF:

0.0251

Gnomad EAS exome

AF:

0.249

Gnomad FIN exome

AF:

0.0570

Gnomad NFE exome

AF:

0.0574

Gnomad OTH exome

AF:

0.0681

GnomAD4 exome

AF:

0.0635

AC:

92781

AN:

1461142

Hom.:

4309

Cov.:

AF XY:

0.0652

AC XY:

47392

AN XY:

726870

show subpopulations

African (AFR)

AF:

0.0905

AC:

3031

AN:

33476

American (AMR)

AF:

0.0885

AC:

3956

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.0242

AC:

632

AN:

26130

East Asian (EAS)

AF:

0.247

AC:

9818

AN:

39692

South Asian (SAS)

AF:

0.134

AC:

11527

AN:

86246

European-Finnish (FIN)

AF:

0.0590

AC:

3125

AN:

52946

Middle Eastern (MID)

AF:

0.0347

AC:

200

AN:

5764

European-Non Finnish (NFE)

AF:

0.0505

AC:

56137

AN:

1111806

Other (OTH)

AF:

0.0721

AC:

4355

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

5726

11452

17178

22904

28630

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0764

AC:

11633

AN:

152302

Hom.:

605

Cov.:

AF XY:

0.0799

AC XY:

5950

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.0921

AC:

3830

AN:

41568

American (AMR)

AF:

0.0856

AC:

1310

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0271

AC:

AN:

3470

East Asian (EAS)

AF:

0.256

AC:

1323

AN:

5158

South Asian (SAS)

AF:

0.137

AC:

662

AN:

4824

European-Finnish (FIN)

AF:

0.0526

AC:

559

AN:

10630

Middle Eastern (MID)

AF:

0.0510

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0537

AC:

3654

AN:

68028

Other (OTH)

AF:

0.0619

AC:

131

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

560

1120

1679

2239

2799

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0546

Hom.:

105

Bravo

AF:

0.0757

Asia WGS

AF:

0.195

AC:

676

AN:

3478

EpiCase

AF:

0.0455

EpiControl

AF:

0.0439

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 09, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Ile27Ile in Exon 04 of ESRRB: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 8.1% (301/3718) of Af rican American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs35544003). -

not provided

Benign:2

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Autosomal recessive nonsyndromic hearing loss 35

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.23

CADD

Benign

4.4

(source)

DANN

Benign

0.91

PhyloP100

-0.31

PromoterAI

-0.021

Neutral

(source)

Mutation Taster

=98/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs35544003

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over